Site-Selective Ruthenium-Catalyzed C-H Bond Arylations with Boronic Acids: Exploiting Isoindolinones as a Weak...

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• N-arylisoindolinones are important scaffolds in medicinal chemistry.
• Efficient methods for C-H functionalization are crucial for streamlining synthesis.
• Ruthenium catalysis offers unique reactivity for C-H bond activation.

Purpose of the Study:

• To develop a novel ruthenium-catalyzed arylation method for N-arylisoindolinones.
• To investigate the selectivity and scope of the C-H functionalization reaction.
• To demonstrate the utility of this methodology for late-stage functionalization.

Main Methods:

• Ruthenium-catalyzed C-H bond functionalization using N-arylisoindolinones.
• Employing boronic acids and potassium aryltrifluoroborates as coupling partners.
• Optimization of reaction conditions for high yield and selectivity.

Main Results:

• Efficient and selective monoarylation of N-arylisoindolinones via C-H functionalization.
• Exclusive ortho-selectivity observed on the nitrogen-linked aromatic ring.
• High functional group tolerance demonstrated with various substrates.
• Successful late-stage functionalization of indoprofen.

Conclusions:

• A novel and efficient ruthenium-catalyzed arylation of N-arylisoindolinones has been established.
• The method provides a valuable tool for accessing diverse N-arylisoindolinone derivatives.
• The demonstrated late-stage functionalization capability offers significant potential in drug discovery and development.